Format

Send to

Choose Destination
See comment in PubMed Commons below
Scand J Rheumatol. 2014;43(1):35-42. doi: 10.3109/03009742.2013.808375. Epub 2013 Aug 28.

The hURAT1 rs559946 polymorphism and the incidence of gout in Han Chinese men.

Author information

1
Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University Medical College , Qingdao , China.

Abstract

OBJECTIVES:

Our previous study identified rs559946, a human urate transporter 1 (hURAT1) single nucleotide polymorphism (SNP), as being significantly associated with risk of primary hyperuricaemia (HUA) in a Han Chinese population. In the current study we aimed to identify the genetic effects of rs559946 on gout susceptibility in Han Chinese men.

METHOD:

A total of 335 patients with gout and 376 healthy controls were recruited for a case-control association study. To examine the functional effect of rs559946, we performed luciferase reporter assays and an electrophoretic mobility shift assay (EMSA).

RESULTS:

rs559946 was found to be significantly associated with gout susceptibility (p = 0.004), with T-allele carriers showing a decreased risk of gout [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.89]. Multiple linear regression analysis identified a significant association between rs559946 genotypes and tophi. Luciferase reporter assays show increased transcriptional activity of the hURAT1 promoter with the C allele of rs559946. EMSA detected binding of nuclear proteins to both the T and C alleles, although increased binding was observed with the T allele. Cold competition assays suggest that rs559946 may bind within a glucocorticoid receptor (GR) binding motif.

CONCLUSIONS:

Our study suggests that the rs559946 polymorphism is associated with increased HUA risk and may also contribute to gout development in Han Chinese men. The T to C substitution within rs559946 increased the transcriptional activity, and potentially increases gout susceptibility.

PMID:
23981340
DOI:
10.3109/03009742.2013.808375
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis
    Loading ...
    Support Center